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PubMed2026

Efficacy and Safety of Autologous Versus Prosthetic Grafts in the Repair of Popliteal Artery Aneurysms: A Systematic Review and Meta-Analysis.

BACKGROUND: Popliteal artery aneurysms (PAAs) present a severe risk of progression to acute limb ischemia. Open surgery (OS) is the gold standard treatment; however, prosthetic grafts are acceptable in highly selected cases, especially when the great saphenous vein is not available. METHODS: We performed a systematic review and meta-analysis of studies comparing autologous versus prosthetic grafts for patency and limb preservation outcomes in patients with PAAs. MEDLINE, Embase, and Cochrane Central were systematically searched from inception through October 2024. Outcomes were pooled using a frequentist random-effects model as odds ratios, mean differences, and hazard ratios (HRs) with 95% confidence intervals (CIs) on RStudio (Version 4.5.0). Risk-of-bias assessments were performed using ROBINS-I and MINORS. RESULTS: Twenty-two observational studies were pooled comprising 9,145 PAAs in 8,370 patients, of whom 6,434 (74.51%) were treated with autologous grafts and 2,200 (25.49%) with prosthetic grafts. Follow-up ranged from 12 to 86 months. Repair with autologous conduits significantly improved long-term primary patency (HR 3.93; P < 0.001), secondary patency (HR 6.02; P < 0.001), and long-term limb salvage (HR 2.69; P = 0.044) compared with prosthetic conduits. There were no significant differences in in-hospital amputation (P = 0.36), myocardial infarction (P = 0.61), mortality (P = 0.50), 2-year primary patency (P = 0.25), 5-year secondary patency (P = 0.06), or length of hospital stay (P = 0.95). Risk of bias was classified as moderate-to-high, reflecting confounding factors inherent to observational studies and moderate methodological quality by MINORS. Despite these limitations, treatment effects consistently favored autologous grafts in both short- and long-term analyses; however, caution is warranted given the limited number of available studies. CONCLUSION: The use of autologous conduits significantly favors both short-term and long-term efficacy and safety in the OS repair of PAAs. Given the limitations of the existing evidence, further comparative studies are needed.

Humans↗

PubMed2026

Effect of atenolol versus ivabradine on heart rate variability in patients of schizophrenia with clozapine-induced tachycardia: a randomized controlled trial.

BACKGROUND: A third of schizophrenia cases are resistant to antipsychotics, where clozapine is the only FDA-approved medication. Clozapine use is often limited by intolerable adverse effects. Persistent tachycardia occurs in approximately 25-54% patients receiving clozapine. Heart rate variability (HRV) is a non-invasive, clinically relevant marker of autonomic nervous system functioning. Atenolol and Ivabradine are usually prescribed for clozapine-induced tachycardia (CIT), although evidence guiding their optimal use remains limited. AIM: This study aimed to compare the effects of atenolol versus ivabradine on HRV in patients with treatment-resistant schizophrenia (TRS) receiving clozapine. METHODS: This open-label randomised clinical trial, conducted at a tertiary-care center over 20 months, involved TRS patients on clozapine for more than three months and having persistent tachycardia. Twenty patients received atenolol 25mg once-daily, while twenty received ivabradine 5mg twice-daily for two months. The primary outcome was the change in the frequency domain of HRV, while the secondary outcomes were time-domains, central and peripheral blood pressure, pulse rate and treatment-emergent adverse events (TEAE). RESULTS: While both drugs significantly reduced pulse-rates (atenolol: -20.56±13.00, p<0.001; ivabradine: -21.855±12.873, p<0.001). Within-group analysis showed that, the atenolol group had significant improvements in high-frequency [HF] power (p=0.048) and LF/HF ratio (p=0.044), along with a non-significant trend towards increased total power (p=0.053); no significant within-group changes were observed in the ivabradine group. CONCLUSION: No significant between-group differences in HRV parameters were established between atenolol and ivabradine. Ivabradine could be a viable option in patients where atenolol is either contraindicated or not tolerated. Future larger multicentric studies are needed for greater generalisability. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT06505668.

Humans↗

PubMed2026

Smartphone apps for obesity management: A systematic review using self-determination theory.

BACKGROUND: While bariatric surgery and pharmacotherapy are effective treatments for obesity, ongoing supportive care remains a challenge. Smartphone applications (apps) may assist with symptom management, but their effectiveness and practical use in obesity treatment is unclear. This review evaluated the effectiveness, acceptability, and feasibility of these apps in supporting individuals following obesity treatment. To better understand how these apps may promote sustained engagement and behaviour change, their design was analysed using Self-Determination Theory (SDT). METHODS: A systematic search was conducted across MEDLINE, Embase, PsycINFO, CINAHL, Web of Science, SCOPUS, and CENTRAL databases. Eligible studies included randomised and non-randomised interventions involving adults (≥18 years) with obesity (BMI ≥ 30 kg/m2) who had undergone bariatric surgery or pharmacotherapy. Interventions had to include an app designed to support post-treatment symptom management. Findings were synthesised narratively, and app features were mapped to SDT constructs of autonomy, competence, and relatedness. RESULTS: Five studies (three RCTs, two cohort studies) involving 1,133 participants were included (female: 78 %; median age: 47.63 years). Most apps targeted post-bariatric surgery care; only one focused on pharmacotherapy. Common features included tracking, reminders, and education, supporting autonomy and competence. Relatedness features such as communication and peer support were least represented. Two studies reported improvements in weight-related outcomes and one in medication adherence. Effects on quality of life, self-efficacy, and healthcare utilisation were not significant. Patient satisfaction was reported in one study, with 95 % expressing positive feedback, though formal assessments of feasibility and acceptability were limited. CONCLUSION: Smartphone apps show potential to support obesity management, particularly after bariatric surgery. While some evidence suggests benefits for weight loss and adherence outcomes, the limited studies and variability of reporting prevent conclusive observations in other outcomes. Future app development should integrate behavioural theory to address psychological needs, nutritional risks and promote holistic self-management beyond weight control.

Female↗

PubMed2026

Exploring the experiences, views, and needs of family members of emergency response workers: a systematic review and meta-synthesis.

Background: Emergency responders, including firefighters, police officers, and paramedics, face workplace challenges that may harm their well-being. They typically rely on family members for support, which may have damaging effects on the family system. While the experiences of emergency responders are well established, their families' subsequent struggles are less well explored.Objective: This review explores the experiences, views, and needs of family members, through determining the mental health and well-being issues that they face, and establishing ways in which family members could be supported.Method: We searched five databases (MEDLINE, Embase, PsychINFO, Scopus, and ProQuest) for qualitative papers exploring experiences of family members of emergency responders. Seventeen studies met the inclusion criteria, and data were meta-synthesized using thematic analysis.Results: Six themes and two subthemes were identified from the meta-synthesis. 'Experiences of emotional strain' reflected worry over safety and coping with volatile moods. 'Increased responsibilities' involved safeguarding emergency responders' well-being and managing household duties, at the expense of family members' own needs. Families felt 'devoted yet invisible', with sacrifices overlooked by both emergency responders and society. 'Impacts on the family dynamic' included relational detachment and frustration. 'Support for emergency responder families' from fellow emergency responder families was valued, but organizational support was limited. 'Media portrayal and societal perceptions' varied, as police families faced hostility, while firefighter and paramedic families garnered respect, particularly during the COVID-19 pandemic.Conclusions: This review highlights that family members play a central role in maintaining the well-being of emergency responders, yet simultaneously face hardships associated with their family member's work and feel undervalued despite their support. This lack of recognition extends to limited professional support. There is a critical need for targeted mental health interventions to support family members, alongside family support measures from emergency responder organizations to assist with the practical difficulties faced by families.

Humans↗

PubMed2026

Characteristics of p53 and Smad4 immunohistochemistry in pancreatic ductal adenocarcinoma and validation by next-generation sequencing.

BACKGROUND: Mutations in four major driver genes -KRAS, CDKN2A, TP53, and SMAD4- are central to the pathogenesis of pancreatic ductal adenocarcinoma (PDAC) and critically inform diagnosis, therapeutic decision-making, and prognostic assessment. Although next-generation sequencing (NGS) is widely regarded as the gold standard for detecting these mutations, its clinical application is often limited by suboptimal analytical efficiency and substantial economic cost. Among these genes, immunohistochemical (IHC) staining for the proteins encoded by TP53 and SMAD4 has been extensively adopted in routine pathology practice. However, standardized IHC pattern classification schemes and rigorous validation of their predictive accuracy for underlying genomic alterations remain lacking in PDAC. METHODS: We retrospectively enrolled 63 PDAC patients and systematically characterized the typical IHC expression patterns of p53 and Smad4. Targeted NGS was subsequently performed on all available tumor specimens, and the resulting mutational profiles were correlated with corresponding IHC findings. Diagnostic performance including sensitivity, specificity and accuracy of p53 IHC for predicting TP53 mutations and of Smad4 IHC for predicting SMAD4 mutations was rigorously evaluated. RESULTS: Among the four canonical driver genes, co-occurring double- or triple-gene mutations were prevalent; within TP53 and SMAD4, missense mutations constituted the most frequent variant type. Using NGS as the reference standard, we validated the diagnostic utility of a three-tiered p53 IHC classification system, particularly in fine-needle biopsy (FNB) specimens. Furthermore, we proposed a novel, refined Smad4 IHC pattern classification that incorporates an "intermediate" category, thereby expanding upon conventional binary interpretation. This new scheme achieved markedly improved mutation prediction accuracy (0.76) compared with traditional approaches (0.57). CONCLUSION: Our study highlights the complementary diagnostic value of p53 and Smad4 IHC relative to molecular testing in PDAC, especially when tissue is limited, as commonly encountered in FNB specimens. The newly established Smad4 IHC classification system, which integrates an intermediate expression category into the conventional two-tier framework, demonstrates superior clinical utility and enhances predictive accuracy for SMAD4 genomic alterations.

Humans↗

PubMed2026

Patient experiences of diagnostic uncertainty in musculoskeletal care: a systematic review of qualitative studies.

BACKGROUND: Diagnosis plays a central role in musculoskeletal care. However, establishing a clear diagnosis is often challenging, and diagnostic uncertainty is common. OBJECTIVES: To explore patient experiences of diagnostic uncertainty in musculoskeletal care. METHODS: Five databases (CINAHL, Embase, MEDLINE, AMED, Web of Science) were searched from inception to October 2025. Qualitative studies involving semi-structured interviews with adults receiving care for MSK conditions were included. Methodological quality was appraised using the Joanna Briggs Institute Qualitative Checklist. Data were synthesised using thematic synthesis, and confidence in findings was assessed using the Grading of Recommendations Assessment, Development, and Evaluation Confidence in the Evidence from Reviews of Qualitative Research approach (GRADE-CERQual). RESULTS: Twenty-six studies involving 462 participants were included. Critical appraisal identified 23 studies with varying methodological limitations; all studies were included in the synthesis. Nine descriptive themes were synthesised into three analytical themes: (1) patient expectations and perceived meanings of a diagnosis and interpretations of diagnostic uncertainty; (2) the multi-dimensional experience of diagnostic uncertainty; and (3) the role of contextual factors, particularly communication and the therapeutic relationship, in shaping experiences of diagnostic uncertainty. Using GRADE-CERQual, confidence in these themes was rated as low, moderate and very low, respectively. CONCLUSION: Diagnostic uncertainty is a subjective and multi-dimensional experience shaped in part by patients' expectations and the meanings attributed to diagnosis. Its impact spans predominantly cognitive and affective domains and may influence clinical presentation. Patient-centred communication and strong therapeutic relationships may support patients in navigating diagnostic uncertainty in musculoskeletal care.

Adult↗

PubMed2026

Descemet Stripping Only in Fuchs Endothelial Corneal Dystrophy: Results of a Randomized Clinical Trial of Topical Ripasudil and Directions for Future Innovation.

PURPOSE: To review history of Descemet stripping only (DSO) in Fuchs endothelial corneal dystrophy, describe the results of a clinical trial of topical ripasudil after DSO (K-321-201 study), and discuss future directions. METHODS: A 1-year, phase 2, randomized, placebo-controlled multicenter clinical trial of two doses of K-321 (ripasudil) administered for 12 weeks after DSO surgery in Fuchs endothelial corneal dystrophy was performed. The primary endpoint, central corneal endothelial cell density (ECD) at 12 weeks after surgery, was determined by an independent reading center that was masked to study group assignment. Duration of corneal edema, need for medical or surgical rescue therapy, corneal thickness, and central ECD throughout the entire study period were also examined. Adverse events and exploratory endpoints were collected. RESULTS: Sixty-five subjects were enrolled (21 in the QID group, 22 in the BID, and in the placebo group). Over 95% of subjects completed the trial. The QID group had a higher central ECD 12 weeks after DSO than the placebo group (531 ± 312 cells/mm2 vs 228 ± 298 cells/mm2, P = .0065). Corneal edema cleared in 17/21 (81.0%) of the QID group at 12 weeks, compared with 2/22 (9.1%) of the placebo group (P < .0001). Rescue was required in 2/21 (9.5%) subjects in the QID group and 6/22 (27.3%) subjects in the placebo group (P = .0092). Adverse events were mild and did not lead to discontinuation of treatment. CONCLUSIONS: Topical K-321 given QID improves DSO outcomes, as demonstrated by a higher ECD, more rapid resolution of corneal edema, and reduced failure rate. The medication was well-tolerated.

Humans↗

PubMed2026

Comparative Bioavailability of Trimodal (CTx-1301) Versus Bimodal Dexmethylphenidate Modified-Release Formulations in Adults with Attention-Deficit/Hyperactivity Disorder: A Randomized, Single-Dose, Crossover Study.

BACKGROUND AND OBJECTIVES: Attention-deficit/hyperactivity disorder (ADHD) is a chronic neurodevelopmental disorder that often requires sustained symptom control throughout the day. Although bimodal extended-release dexmethylphenidate (d-MPH XR) formulations provide initial and intermediate drug release, they may not consistently maintain therapeutic exposure into the late afternoon and evening. Trimodal formulations with an additional delayed release component may extend drug exposure later in the day, although this remains to be established. To explore differences in pharmacokinetic (PK) profiles between trimodal (CTx-1301) and bimodal delivery of d-MPH XR, a comparative bioavailability study was conducted at the highest and lowest doses for both formulations. METHODS: In this randomized, 4-period, crossover study, adults with ADHD received single doses of CTx-1301 (50 mg and 6.25 mg) and d-MPH XR (40 mg and 5 mg). Comparative bioavailability was assessed through adjusted geometric mean ratios for exposure parameters (maximum observed plasma concentration [Cmax], area under plasma concentration-time curve to last measurable concentration [AUClast] and extrapolated to infinity [AUC0-inf]), with a prespecified bioequivalence range of 0.80 to 1.25. Secondary endpoints included partial AUCs and safety assessments. RESULTS: The study population (N = 45) was predominantly male (88.9%) and White (55.6%), with mean age of 29.6 ± 8.01 years. Adjusted geometric mean ratios comparing the primary exposure parameters (Cmax, AUClast, and AUC0-inf) for CTx-1301 versus d-MPH XR were within the bioequivalence range (0.80-1.25) at both the high and low doses. The CTx-1301-to-d-MPH XR partial AUC ratios were within the bioequivalence range from 0 to 9 hours post-dose. At later intervals (AUC9-12 and AUC12-16), adjusted geometric mean ratios exceeded the upper bioequivalence threshold, consistent with the expected contribution of the third medication release component. Dose proportionality was observed between the two CTx-1301 doses and two d-MPH XR formulations. CTx-1301 was generally well tolerated. The most commonly reported adverse events included tachycardia, insomnia, headache, nausea, and euphoric mood. The incidence of treatment-emergent adverse events was numerically lower with CTx-1301 than with d-MPH XR; however, no statistical analysis was performed. CONCLUSIONS: Key exposure parameters including Cmax, AUClast, and AUC0-inf for trimodal CTx-1301 were statistically bioequivalent to bimodal d-MPH XR. Interval‑specific PK analyses demonstrated higher exposure with CTx‑1301 during later post-dose intervals (9-16 h), consistent with the formulation's third release component. However, the clinical relevance of these PK differences requires further evaluation. CTx-1301 demonstrated dose proportionality and was well tolerated at high and low doses. REGISTRATION: ClinicalTrials.gov, NCT04138498; 19 September 2019.

Humans↗

PubMed2026

Association between prenatal exposure to tetrachloroethylene and adverse birth outcomes: Systematic review and meta-analysis.

BACKGROUND: Tetrachloroethylene (PCE) is a ubiquitous chlorinated solvent with documented placental transfer. Despite widespread environmental and occupational exposure, no prior systematic review has synthesized evidence on prenatal PCE exposure and adverse birth outcomes. METHODS: We conducted a systematic review and meta-analysis of observational studies. PubMed, Web of Science, PsycINFO, EMBASE, and CINAHL were searched from inception to July 13, 2026. Eligible studies reported associations between prenatal PCE exposure (drinking water or inhalation) and adverse birth outcomes. Study quality was assessed using the Newcastle-Ottawa Scale (NOS) and Agency for Healthcare Research and Quality (AHRQ) criteria. Random-effects meta-analyses were performed using risk ratios (RRs) with 95% confidence intervals (CIs), with Knapp-Hartung adjustments and Paule-Mandel τ2 estimation. RESULTS: Twenty one studies (1987-2023) met inclusion criteria. Prenatal PCE exposure was associated with spontaneous abortion (8 studies; RR = 1.28, 95% CI 1.00-1.63; I2 = 64.2%). Analyses of stillbirth, central nervous system defects, oral clefts, neural tube defects, preterm birth, low birthweight, and small-for-gestational-age (SGA) yielded positive but statistically non-significant pooled estimates. The certainty of evidence ranged from very low to low across outcomes (GRADE). CONCLUSIONS: Prenatal PCE exposure may be associated with spontaneous abortion, particularly at higher exposure levels, and with SGA. Findings support ongoing regulatory efforts to limit PCE in occupational and environmental settings, particularly for pregnant individuals. Future prospective studies with biological monitoring and confounder-adjusted designs are needed.

Tetrachloroethylene↗

PubMed2026

Control of foreign DNA: emerging roles of xenogeneic silencers.

Bacteria continuously acquire foreign DNA through horizontal gene transfer, yet its successful integration depends on regulatory mechanisms that balance genome protection with evolutionary innovation. Xenogeneic silencers are central to this process: they preferentially bind AT-rich DNA, a common feature of many horizontally acquired genetic elements, and repress its transcription. Recent studies, however, reveal a much broader regulatory repertoire. Beyond transcriptional repression, these proteins contribute to chromosome organization by forming higher-order nucleoprotein complexes and phase-separated condensates that shape bacterial nucleoid architecture. Furthermore, they play roles in regulating bacteriophage infection cycles, including mechanisms by which phages hijack host silencing activities for their own benefit. Their extensive regulatory reach, spanning virulence genes, biofilm formation, specialized metabolite production, and mobile genetic elements (MGEs), underscores their central role in connecting environmental signals, including fluctuations in the second messenger c-di-GMP, with gene expression, and genome organization. The diversification of xenogeneic silencers across bacterial chromosomes, plasmids, phages, and other MGEs highlights their evolutionary significance. Together, these recent findings position xenogeneic silencers as dynamic regulatory modules that shape the fate of foreign DNA across the horizontal gene transfer network.

Gene Transfer, Horizontal↗

PubMed2026

Meaning in Life in Palliative Cancer Care: Psychosocial and Existential Outcomes-A Systematic Review.

BackgroundExistential distress, marked by hopelessness, loss of meaning, and spiritual suffering, is prevalent among patients with advanced illness, and is associated with psychological burden and a wish to hasten death (WTHD).PurposeThis systematic review aimed to synthesize current evidence on meaning in life (MIL) in adult palliative care (PC) populations, focusing on its associations with quality of life (QOL), mental health, existential and spiritual well-being (SWB), and WTHD.MethodsMEDLINE, Web of Science, Scopus, and the Cochrane Library were searched for eligible studies (English, 2016-2024) involving adult cancer patients receiving PC. MIL was examined as a central intervention component or outcome. Risk of bias was assessed: findings were synthesized narratively. The review was registered in PROSPERO.ResultsEight studies (n = 1733 participants) were included: four cross-sectional, two randomized controlled trials, one longitudinal observational study, and one qualitative study. Several studies had small samples and substantial attrition. Risk of bias was high (n = 7), and moderate in one cross-sectional study. MIL was inversely associated with depression, anxiety, demoralization, and WTHD; and positively associated with QOL and SWB. MIL may also mediate psychological outcomes (eg, purpose, coherence, and personal values). However, heterogeneity in MIL conceptualization and measurement, combined with low methodological quality, limited comparability and certainty of findings.ConclusionMIL may be relevant to psychosocial/existential outcomes in PC. Conclusions are constrained by a small and methodologically weak evidence base. Further high-quality, longitudinal research is needed before MIL-centered interventions can be recommended for routine clinical practice.

Humans↗

PubMed2026

Natural deep eutectic solvent in situ formation-based extraction method coupled to high-performance anion-exchange chromatography with pulsed amperometric detection for multiclass carbohydrates in hot pot bases.

A novel method was developed for the simultaneous extraction of fourteen multiclass carbohydrates from high-fat foods via the in situ formation of deep eutectic adducts from analytes and acetate ions. Different natural deep eutectic solvents (NADESs) composed of fructose and organic acids were tested as extraction solvents. A model NADES formulated with sodium acetate and fructose was characterized using Fourier transform infrared (FTIR) spectroscopy and hydrogen nuclear magnetic resonance (1H-NMR) spectroscopy. The critical extraction parameters were systematically optimized using multi-response surface methodology (MRSM) with a central composite design (CCD). The extract was analyzed using high-performance anion-exchange chromatography coupled with pulsed amperometric detection (HPAEC-PAD) using a sodium hydroxide-sodium acetate eluent, which did not require organic solvents. This approach exhibited good linearity over the concentration range of 0.02-10 mg L-1, with correlation coefficients (r) ranging from 0.9994 to 0.9999. The limits of detection and quantification were in the ranges of 0.06-0.42 mg kg-1 and 0.19-1.3 mg kg-1, respectively, which were significantly lower than those of liquid chromatography (LC). The protocol was successfully applied to the determination of fourteen carbohydrates in forty-five hotpot seasoning samples. The recoveries ranged from 86.3% to 104.1%, with relative standard deviations (RSDs) of 0.9-7.1%. By integrating multiple techniques, this strategy simplifies operations, shortens extraction time, and achieves baseline separation of three carbohydrate classes that exhibit poor resolution using a conventional LC method. This study describes an efficient procedure for the simultaneous determination of multiple trace-level carbohydrates in complex samples using HPAEC-PAD.

Journal Article↗

PubMed2026

Association Between Statin Use and Dry Eye Disease: A Systematic Review and Meta-Analysis.

TOPIC: This systematic review and meta-analysis evaluated the literature-pooled association between statins and dry eye disease (DED). CLINICAL RELEVANCE: Statins, a common treatment modality for dyslipidemia, have been proposed as a potential contributor to DED via their activity in meibomian gland epithelial cells. However, single studies show mixed evidence, and there remains an unmet clinical need to clarify whether statin exposure is associated with DED. METHODS: This review was reported in accordance with the Preferred Reporting Items for Systematic Reviews of Interventions (PRISMA) 2020 statement and was registered a priori on PROSPERO (CRD420251238004). Ovid MEDLINE, Embase, CINAHL, Web of Science, CENTRAL, and the reference lists of relevant reviews were searched from inception to November 2025 for studies reporting the association between statin use and DED. Random-effects meta-analysis using inverse-variance weighting was conducted to pool effect estimates as odds ratios with 95% confidence intervals (CIs). Study risk of bias was appraised using the ROBINS-E tool, and the certainty of the evidence was reported using the GRADE framework. RESULTS: Six observational studies were included in the meta-analysis (n = 560,821; 356,012/559,141 [63.7%] statin users). The pooled analysis revealed a significant positive association between statins and DED (odds ratio 1.09, 95% CI 1.05-1.13, P < .001), with an absolute risk difference of 10.2 more DED cases per 1000 (95% CI 5.5 more to 15.2 more). This result was derived from very low-certainty evidence given limitations in study design and serious inconsistency. Subgroup and sensitivity analyses for risk of bias (P = .123), method of outcome ascertainment (P = .737), type of effect estimate (P = .496), and leave-one-out analyses showed no evidence of effect modification and demonstrated consistent direction of association across studies. CONCLUSION: Statin use was associated with a small but statistically significant increase in DED, limited by very low-certainty evidence. Physicians should monitor for and educate patients on ocular surface symptoms in patients using statins with pre-existing DED risk factors. Future studies should use standardized DED diagnostic criteria to investigate the impact of statin dose, type, and duration to better characterize this potential association.

Humans↗

PubMed2026

Pharmacological and non-pharmacological modulation of striatal dopamine release: a meta-analysis of [11C]raclopride PET studies.

The dopaminergic system has long been a central focus of functional neuroimaging. Positron emission tomography (PET) with the D2/D3 receptor radioligand [11C]raclopride remains the most widely used method for indirectly quantifying striatal dopamine release in vivo. However, no previous meta-analysis has studied the relative magnitude and regional distribution of dopamine release across different interventions or cognitive interventions overall. To address this gap, in this meta-analysis of 92 [11C]raclopride PET studies (n = 1640), we compared the magnitude and regional distribution of dopamine release induced by amphetamine, methylphenidate, ketamine, alcohol, and cognitive challenges with and without reward. Amphetamine induced approximately four-fold greater dopamine release than cognitive challenges (10.9 vs. 2.7%, p < 0.001), and approximately twice that of alcohol (4.8%, p < 0.001), with effects comparable to methylphenidate (11.5%) and slightly greater than ketamine (9.8%). Psychostimulant-induced increase in synaptic dopamine was greater in putamen and ventral striatum than in caudate, whereas alcohol preferentially engaged ventral striatum. Dopamine release did not differ between rewarded and non-rewarded cognitive tasks in the ventral striatum (p > 0.14) or overall striatum (p > 0.10). Methylphenidate-induced increases in synaptic dopamine appeared to attenuate with advancing age, whereas cognitive challenges were associated with greater dopamine release in older individuals. These findings demonstrate that individual pharmacological and cognitive interventions differ markedly in both magnitude and regional pattern of dopamine release. They also suggest that [¹¹C]raclopride PET may have limited sensitivity for distinguishing reward-related from non-reward-related dopamine release. These findings have implications for the design and interpretation of future neuroimaging studies of dopaminergic function in health and disease.

Journal Article↗

PubMed2026

An expanded breakfast buffet increases daily energy and protein intakes in hospitalised patients: A prospective crossover quality improvement study.

BACKGROUND & AIMS: Inadequate dietary intake remains common during hospitalisation. Ordinary hospital meals are central to nutritional intake, but their contribution depends on what is offered and what patients are able and willing to eat. We evaluated whether a preference-informed, limited expansion of the hospital breakfast buffet could increase total daily energy and protein intakes. METHODS: This prospectively structured, ward-based crossover quality-improvement study was conducted in seven inpatient wards at a tertiary university hospital. Each ward was observed for four consecutive days and randomly allocated to begin with standard or expanded breakfast, after which conditions alternated daily. The expanded buffet consisted of standard breakfast supplemented with familiar energy- and protein-rich foods selected from previous patient-choice data. Twenty-four-hour intake was registered using component-level weighed food records during the day and nursing registration overnight. Primary outcomes were total daily energy and protein intakes. Linear mixed-effects models adjusted for observation day and ward-level starting sequence and accounted for repeated patient observations and ward-level clustering. Analyses used data from patients who consumed breakfast and contributed analysable observations under both breakfast conditions. RESULTS: The primary crossover population included 71 patients contributing 188 analysable patient-days. Compared with standard breakfast, the expanded breakfast increased total daily energy intake by +198 kcal/day (95% CI 44 to 352) and protein intake by +6.8 g/day (95% CI 1.0 to 12.5), without a statistically significant increase in total food weight. Daily energy and protein adequacy increased by +8.7 and + 6.8 percentage points, respectively. The increase was driven mainly by breakfast intake, with no measurable reduction in non-breakfast intake. CONCLUSIONS: A limited expansion of the ordinary hospital breakfast buffet increased total daily energy and protein intakes in the primary crossover population of hospitalised adults who consumed breakfast. This increase occurred without a statistically significant increase in total food weight or a measurable reduction in non-breakfast intake. Small, preference-informed additions of familiar energy- and protein-rich foods at breakfast may improve daily intake by increasing the nutrient yield of foods patients are able or willing to eat.

Humans↗

PubMed2026

Gelified ethanol for percutaneous sclerotherapy of bone lesions: a systematic review of clinical applications and outcomes.

PURPOSE: To systematically review the available evidence on the feasibility, safety, and clinical effectiveness of percutaneous sclerotherapy using radiopaque gelified ethanol (RGE, Discogel®) for bone lesions. METHODS: A systematic search of MEDLINE, Embase, Web of Science, and Cochrane CENTRAL was performed. Primary studies reporting clinical, technical, and safety outcomes following RGE sclerotherapy for bone lesions were included. Data on patient characteristics, lesion type, procedural details, and outcomes were extracted and synthesized descriptively. RESULTS: Six retrospective studies involving 55 patients (mean age 22.2 ± 20.4 years; range 3-65; 26 females) with 56 lesions and 119 procedures were included (mean 2.16 procedures per patient). Aneurysmal bone cysts (80%) and aggressive vertebral hemangiomas (18%) were the main indications. Technical success was reported in 100% of procedures. Pain outcomes were available for 28 patients, with complete resolution in 64.3% (18/28), partial reduction in 32.1% (9/28), and persistence in 3.6% (1/28). Radiological follow-up (50 lesions) demonstrated complete response in 96% and partial response in 4%. No major adverse events were reported according to CIRSE (≥ 4) or CTCAE (≥ 4) criteria. One SIR grade 3 vertebral fracture occurred without confirmed causal association to RGE. Subsequent surgery was required in 3.6% of lesions. CONCLUSION: Although limited to small retrospective series, current evidence suggests that RGE sclerotherapy is a safe and effective minimally invasive option for selected benign bone lesions. Prospective comparative studies with longer follow-up are warranted.

Humans↗

PubMed2026

The Impact of PCSK9 Inhibitors on Development of Retinal Vascular Occlusions.

PURPOSE: PCSK9 inhibitors (PCSK9i) are a newer class of lipid-lowering drug that may be effective at lowering risk for retinal artery occlusion (RAO) and retinal vein occlusion (RVO). This study aims to investigate the relationship between PCSK9i use and retinal vascular occlusion among patients with hyperlipidemia. DESIGN: Retrospective, comparative clinical cohort study SUBJECTS, PARTICIPANTS, AND/OR CONTROLS: Patients with hyperlipidemia, defined as serum low-density lipoprotein level of ≥130 mg/dL and total cholesterol level of ≥220 mg/dL, prescribed a lipid-lowering medication were identified. Patients prescribed a PCSK9i were included in the study group and compared with control patients prescribed any other type of lipid-lowering drug. METHODS: This study was conducted using electronic health record data from health organizations in the United States through the TrinetX platform. Propensity score matching was completed based on relevant patient demographics, comorbidities, and laboratory values. Comparison of main outcomes between the PCSK9i and non-PCSK9i groups was performed using measures of association analysis to determine risk ratio (RR) with 95% CI. MAIN OUTCOME MEASURES: The outcomes measured consisted of occurrence of retinal vascular occlusion, RAO, RVO, central RAO, and central RVO at 3-year, 5-year, and 7-year time points. RESULTS: After propensity score matching, a total of 12,960 patients were included in each cohort. The analysis revealed that the PCSK9i cohort had a significantly lower risk for development of retinal vascular occlusions at multiple points, including 3-year (RR = 0.56, CI = 0.39-0.79), 5-year (RR = 0.50, CI = 0.37-0.67), and 7-year (RR = 0.46, CI 0.35-0.61) time points. This lower risk was also found in the PCSK9i group for an outcome of RVO at 5 years (RR = 0.50, CI = 0.34-0.73) and 7 years (RR = 0.47, CI = 0.33-0.67). For occurrence of RAOs (RR = 0.47, CI = 0.30-0.76) and central RVO (RR = 0.46, CI = 0.29-0.74) separately, the PCSK9i cohort had a lower risk at 7 years. CONCLUSION: These findings suggest that PCSK9i may reduce the risk of retinal vascular occlusion compared with other classes of lipid-lowering medications.

Humans↗

PubMed2026

Neuroimaging anxious children and adolescents before and after cognitive behavioral therapy: a systematic review.

OBJECTIVE: This systematic review investigates brain changes in youths with anxiety disorders following cognitive behavioral therapy (CBT) and neural markers that predict CBT responses. METHODS: We conducted a systematic search using the electronic databases PubMed, Web of Science, and ProQuest. The inclusion deadline was set to October 27, 2025. We included fifteen peer-reviewed neuroimaging studies that examined the effects of CBT in youths under 19 years old with a primary clinical diagnosis of an anxiety disorder based on DSM-5 criteria. RESULTS: Although the existing literature is marked by substantial diversity in methods and outcomes, task-related neural response in the anterior cingulate cortex (ACC, 2/8, 25.0%), insula (1/8, 12.5%) increased from pre to post CBT and these changes were further correlated with clinical symptom improvements. Moreover, CBT outcomes were predicted by pre-treatment activity or connectivity in the ACC and amygdala (3/13, 23.0%). A smaller proportion of studies (2/13, 15.3%) found that activity or connectivity in the insula, precuneus/cuneus, postcentral gyrus, and activity or structure in the nucleus accumbens (NAcc) predicted response to CBT. The low consistency of these findings was driven by methodological variability, low reliability of the neural markers, and relatively small sample sizes. CONCLUSIONS: This review highlights promises of neural predictors and outcomes to enhance anxiety disorder treatments in children and adolescents, facilitating future personalized and effective CBT. Beyond this initial promise, the field is hindered by methodological inconsistencies and limited replications. While longitudinal and personalized approaches are important next steps, the central challenge remains: identifying neural markers that are both reliable and robust.

Adolescent↗